The overall goal of this project is to characterize the immune response to HPV infection of the genital tract and to define the role of immune modulation in the progression to malignancy. Serological assays to detect serum IgG antibodies to HPV types 6, 16 and 18 have been developed and form the basis for a new marker of HPV exposure in epidemiologic studies. The specific aims of this study are: 1) To continue characterizing the humoral immune response in greater depth by examining the contribution of antibodies directed against conformational epitopes using yeast expressed proteins and virions made using recombinant vaccinia virus vectors; and continuing to delineate immunoreactive epitopes; 2) To examine HPV specific IgA antibodies present in serum, saliva, and cervicovaginal secretions; 3) To compare the Western blot assay with ELISAs using yeast expressed proteins, virions, or synthetic peptides for screening methods; 4) Populations will be screened for HPV antibodies to determine a) the prevalence of antibodies in the general population and in cases with anogenital cancer; b) immunological markers associated with malignancy; c) risk factors associated with seropositivity; d) the correlation between HPV antibodies and other measures of infection; and 5) To study the cell mediated immune response to HPV infection in lymphoproliferative assays and by identifying cytotoxic T cells. Information about the immune response to HPV infection is essential in epidemiologic studies, in the clinical management of disease, and in the development of vaccines to prevent infection or tumor development.